Safety and efficacy of piroxicam patches for treating knee osteoarthritis / 대한내과학회지

BACKGROUND/AIMS: We wanted to compare the efficacy and safety of a Murupe(R) patch, which is a newly-developed piroxicam patch, with the Trast(R) patch for the treatment of knee osteoarthritis. METHODS: Two hundred ten patients with radiologically confirmed symptomatic osteoarthritis of the knee were included in a randomized, open-labeled controlled trial and they were treated with a 48 mg piroxicam patch once every 48 hours for 4 weeks. The main outcome measures were the pain intensity on movement and the spontaneous pain intensity during rest, and these were measured using the 10 cm Visual Analogue Scale (VAS) categorical pain scores, as measured by the patient and the investigator. RESULTS: One hundred sixty-seven of the 210 enrolled patients completed the 4 week study. The pain intensity on movement was significantly reduced in both the Trast(R) and Murupe(R) groups (p<0.001) after 4 weeks of treatment; the improvement on the VAS was significantly higher in the Murupe(R) group (n=82) than that in the Trast(R) group (n=85) (4.5 cm versus 2.2 cm, respectively, p<0.001). Both treatment groups also showed reductions in all the other parameters of pain intensity, including spontaneous pain intensity during rest, the categorical pain scores and the 15 meter-walking time. There was no difference in adverse events between both groups. CONCLUSIONS: The superior analgesic activity of Murupe(R) patch indicates that the topical route of non-steroidal anti-inflammatory drug (NSAID) administration may be a safe, effective alternative to the oral route for the treatment of knee OA, and that the newly developed NSAID patch with its improved transdermal drug delivery may increase the efficacy of topical NSAIDs.

A case of recurrent Kikuchi-Fujimoto disease with SLE / 대한내과학회지

Kikuchi-Fujimoto disease (KFD) is a rare self-limiting necrotizing lymphadenitis found mainly in young women. Patients typically present with lymphadenopathy and often with a high temperature. The etiology of the disease remains unknown, but various viral infection and autoimmune processes have been postulated to be the cause. One theory proposes that KFD may be a self-limiting form of systemic lupus erythematosus (SLE). This theory is strongly supported by the fact that microscopic features of KFD can be very similar to those found in lupus lymphadenitis. The diagnosis of KFD can precede, postdate or coincide with the diagnosis of SLE. No treatment is usually needed and relapse, although possible, is uncommon. Our case describes a young woman, originally diagnosed as having SLE, who subsequently developed recurrent KFD with axillary lymphadenopathy and fever.

A Case of Acute Leukoencephalopathy in a Patient with Systemic Lupus Erythematosus / 대한류마티스학회지

Up to 70% of patients with systemic lupus erythematosus (SLE) are afflicted with neurologic manifestations. However, there are only a few reports documenting acute leukoencephalopathy in SLE. We describe a 20-year-old woman who was recently diagnosed as SLE, suffering from headache, fever and arthritis. She developed an acute onset of consciousness disturbance with seizure followed by prolonged coma, which recovered completely after 1 month of steroid therapy. Her brain MRI showed diffuse high signal intensity in the periventricular and subcortical white matter on T2-weighted and FLAIR images, whereas cerebral cortex, basal ganglia, and thalamus were spared. Acute leukoencephalopathy may be recognized as a subtype of lupus involving the central nervous system.

Combination treatment with leflunomide and methotrexate in patients with rheumatoid arthritis: the efficacy, safety, and predisposing factors for treatment response / 대한내과학회지

BACKGROUND: Leflunomide, a novel immunoregulatory drug, has been shown to be effective in rheumatoid arthritis (RA) as monotherapy and as combination therapy with methotrexate (MTX). The aims of this study were to investigate the efficacy and safety of combination therapy with leflunomide and MTX in active RA patients and to identify the patients with a better response to this combination. METHODS: The patients received a maintenance dose of 20 mg of leflunomide with or without a loading dose. Parameters for disease activity in RA were measured at baseline and at 12 and 24 weeks after initiation of leflunomide. At 24 weeks, the baseline data from the patients classified as leflunomide responders were compared with data from nonresponders and analyzed to determine the potential predisposing factors for treatment response. RESULTS: A total of 103 patients with RA were included and 93 (90.3%) patients received leflunomide for 24 weeks. At 24 weeks, 67 (65.1%) patients were DAS28 responders; 14 (13.6%) were good responders and 53 (51.5%) moderate responders. At 12 weeks, significant improvements were noticeable in the individual efficacy measures of diseases activity. There were also significant improvements between 12 and 24 weeks in swollen joint count, tender joint count, HAQ disability index, and patients' and physicians' global assessments of diseases activity; but no further improvements in ESR or CRP could be seen after the first 12 weeks. When comparing the baseline data from responders with the nonresponders, patients on a higher MTX dose and patients with a higher disease activity at baseline responded better to leflunomide. However, age, sex, disease duration of RA, functional status, loading dosage of leflunomide, and previous number of DMARDs used did not affect the patients' response to leflunomide. CONCLUSION: Combination therapy with leflunomide and MTX is effective and safe across a wide range of patients, especially those with a high disease activity in spite of treatment with other traditional DMARDs.

Expression of Cell Surface Marker on Human Bone Marrow Derived Stromal Cells during Chondrogenic Differentiation / 대한류마티스학회지

OBJECTIVE: Multipotent bone marrow stromal cells have the ability to differentiate toward a variety of connective tissue lineages including cartilage. The future use of adult mesenchymal stem cells (MSCs) for human therapies depends on the establishment of preclinical studies. Therefore, in this preclinical study we demonstrated the expression of MSC surface markers CD29, CD105, and CD44 on human bone marrow derived stromal cells during chondrogenic differentiation. METHODS: Adult human bone marrow was collected from the iliac crest of 7 donors following informed consent. Mononuclear cells were isolated, incubated in monolayers, and embedded in alginate beads for three-dimensional cultures. Cellualr viability was assessed by MTT assay. Flow cytometry of alginate bead cultures was performed on days 0, 7, 14, 21, and 28 using monoclonal antibody against surface molecules, CD105, CD29, CD44, CD34 and CD45. Total contents of collagen and glycosaminoglycan (GAG) of the alginate beads was measured. SPSS 11.0 was used for data analysis. RESULTS: After 7 days of culture, 89% of the cells expressed the human integrin beta 1 antibody, CD29. The CD29-positive cells remained elevated at 83% on days 28. However, while only 18% expressed the type II TGF-beta receptor endoglin, CD105 on day 7, the CD105-positive cells increased abruptly 65% on day 14 remaining elevated up to day 28. The expression of CD44 was maximal in the first passage cell (63%). High concentration of TGF-beta 3 (10 ng/mL) was more favorable for sustaining cell viability than a low concentration (0.5 ng/mL)(n=4, p= 0.002, day 21). The total contents of collagen and GAG in the MSC-alginate beads increased during the three-dimensional culture (n=4, p=0.02, p=0.006) suggesting its differentiation into a chondrogenic lineage. CONCLUSION: CD29 was expressed earlier than CD105 during chondrogenic differentiation of human bone marrow MSC. CD44 expression was highest in the first passage cells and gradually decreased afterwards.

A Case of Overlap Syndrome of Dermatomyositis and Sjogren's Syndrome associated with IgA Nephropathy / 대한류마티스학회지

An "overlap syndrome" is used to describe patients who have two or more well-defined connective tissue diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and polymyositis. Their coexistence is defined clinically and often by specific serologic tests. We report a case of dermatomyositis associated with IgA nephropathy that had overlapping features of Sjogren's syndrome. This dermatomyositis and Sjogren's overlap is a rarely reported overlap syndrome worldwide.

The Prevalence of Metabolic Syndrome in Patients with Gout: A Multicenter Study

It has been suggested that hyperuricemia and possibly gout are associated with the metabolic syndrome, but there have been no direct studies. This study was undertaken to obtain the prevalence of the metabolic syndrome in patients with gout and to compare it with those from the general population studies. This was a 4-institutional case-historical control study composed of 168 patients with gout. We assessed the prevalence of metabolic syndrome according to the ATP III criteria and compared the prevalence with that of the historical controls. To elucidate the factors in gout that were associated with metabolic syndrome, a multivariate analysis was done. The age-adjusted prevalence of metabolic syndrome in gout patients was 43.6%, which was significantly higher than that of the Korean control population (5.2%) from the previous studies. Patients with gout had more components of metabolic syndrome than did the controls. Body mass index (BMI, OR=1.357 (95%CI 1.111-1.657)) and high density lipoprotein (HDL, OR=0.774 (95%CI 0.705-0.850)) were the variables most significantly associated with the occurrence of metabolic syndrome in gout, but alcohol consumption did not show such associations. Gout is associated with the metabolic syndrome, and furthermore, obesity and dyslipidemia were the factors most associated with the syndrome in these patients.

A Case of Mallory-Weiss Syndrome Complicating Pregnancy in a Patient with Scleroderma

The majority of patients with scleroderma have gastrointestinal involvement, and a few experience gastrointestinal hemorrhage, however, gastrointestinal hemorrhage due to Mallory-Weiss syndrome is very rare. We report upon a 24-year-old pregnant woman with scleroderma who had gastrointestinal hemorrhage due to Mallory-Weiss syndrome.

A Case of Relapsing Polychondritis Associated with Myelodysplastic Syndrome with Erythroid Hypoplasia/Aplasia

Relapsing polychondritis (RP) is a rare multisystem disorder. Myelodysplastic syndrome (MDS) with erythroid hypoplasia/aplasia is a rare form of myelodysplasia. Several cases of RP associated with MDS have recently been described. However, RP associated with MDS with erythroid hypoplasia/aplasia has never been reported. There was only one case report of polymyalgia rheumatica associated with MDS with erythroid hypoplasia/aplasia. In this study, we report a 79-year-old patient with RP, who developed MDS subtype refractory anemia (RA) with erythroid hypoplasia/aplasia, a very characteristic subtype of MDS.

Chondrocyte Viability in the Three Dimensional Culture Using Natural Alginate / 대한류마티스학회지

OBJECTIVE: Articular cartilage has a highly limited capacity to repair because of lack of blood supply. There have been no effective modality to regenerate the articular cartilage and prevent degenerative changes. It is necessary to proliferate the cells in vitro, however the cells lose their phenotype during in vitro monolayer culture. Although it is not enough to increase the number of the cells in the three dimensional culture, it is a effective way to maintain their original phenotype expression. Alginate has been used as a good source of scaffold in chondrocyte three dimensional culture. The objective of this study was to find the most favorable scaffold for chondrocyte viability among various alginate extracted from natural source in chondrocyte three dimensional culture. METHODS: The alginate extracted from brown seaweed, Undaria pinnatifida and sea tangle, Laminaria japonica inhabitating near Korean sea and commercially available alginate were used. Chondrocytes isolated from adult pig were used. Three kinds of chondrocyte-alginate bead were made and incubated for forty-four days. Cellular viability and glycosaminoglycan (GAG) content were measured and compared. SPSS Version 10.0 was used for data analysis. RESULTS: Viability of chondrocyte and GAG content were increased as a function of time. Alginate from brown seaweed, U. pinnatifida appeared more favorable to maintain chondrocyte viability than others. The total GAG content was similar among three kinds of alginate CONCLUSION: Alginate extracted from natural see weed, especially brown seaweed, may be a good source to maintain chondrocyte viability in three dimensional culture.

Lack of association between rheumatoid arthritis and vitamin D receptor polymorphisms in Koreans / 대한내과학회지

BACKGROUND: The purpose of this study was to determine whether the distribution of vitamin D receptor (VDR) polymorphisms in rheumatoid arthritis (RA) patients group is different from that of the control group and whether there is a relationship between VDR genotype and radiographic severity or bone mineral density (BMD) of RA patients. METHODS: The VDR genotype was determined by polymerase chain reaction and digestion with three restriction enzymes Taq I, Apa I and Bsm I in 78 healthy women and 97 female RA patients. Hand X-rays were scored by Larsen's method and bone mineral density was measured by dual energy X-ray absorptiometry (DEXA) in RA patients. RESULTS: VDR genotypic distributions in Koreans were much different from Caucasians in each control and RA patient groups. Especially, "tt" allele and "BB" allele were very rare, prominently differentiating from Caucasians. But within Koreans, no significant difference of VDR genotypic frequency was observed between control group and RA patients group. And there was no significant relationship of VDR genotype with radiographic scores, nor with BMD scores in RA patients. CONCLUSION: The distribution of VDR polymorphisms in Korean RA patients was not different from controls. The VDR polymorphisms correlate neither with the radiographic severity of RA, nor with BMD scores in Korean RA patients.

Diagnostic Value of the Antiperinuclear Factor by Indirect Immunofluorescence Method / 대한진단검사의학회지

BACKGROUND: The antiperinuclear factor (APF) has been reported both as a diagnostic tool and as a prognostic marker for rheumatoid arthritis (RA). Our purpose is to study the diagnostic value of the APF, and to compare the detection method of the indirect immunofluorescence method (IIF) and the citrullinated cyclic peptides enzyme-linked immunosorbent assay (CCP-ELISA). METHODS: A total of 131 patients were included in this study. The APF were measured with both the IIF and ELISA. The IIF and ELISA procedures were carried out following the kit's instructions. The medical records such as C-reactive protein (CRP), erythroid sedimentation rate (ESR), the Ritchie index and diagnosis were reviewed retrospectively. SPSS (version 10.0, SPSS inc., USA) was used for statistical analysis. RESULTS: The patients were 94 with RA, 26 with osteoarthritis, 7 with fibromyalgia syndrome, and 3 with palindromic rheumatism, 2 with gout, 2 with systemic lupus erythematosus, 1 with Behcet's disease, and 7 with non specific rheumatic diseases. The sensitivity and the specificity of the APF test in patients with RA were 93%, and 81%, while those with the rheumatoid factor (RF) were 91% and 63% , suggesting the APF has a higher specificity than RF. The area under the curve of APF was 0.87 (95% confidence interval, 0.79 - 0.95), but RF was 0.77 (95% confidence interval, 0.67- 0.87). The kappa statistics between the two detection methods IIF and ELISA was 0.667 (P=0.000), indicating disagreement between these two methods. The detection sensitivety and specificity of APF-IIF were 89% and 73%, while those of ELISA were 80% and 73%. The area under the curve of APF-IIF was 0.82 (95% confidence interval, 0.72- 0.90), but CCP-ELISA was 0.77 (95% confidence interval, 0.67- 0.86). There was a statistically significant correlation between the APF grade and the clinical parameters such as RF (r=0.503, P=0.000), CRP (r=0.333, P=0.000) and ESR (r=0.261, P=0.003). CONCLUSIONS: Taken together, the APF could play a role in diagnosing RA in addition to RF. APF-IIF showed a higher sensitivity than ELISA.

Korean Medical Insurance System in Rheumatic Diseases / 대한류마티스학회지

Korean resource-based relative value scale (RBRVS) was developed first in 1997 for the alternative of the traditional Korean fee-for-service system. The knowledge about the RBRVS-based fee schedule is necessary to understand the physician payment system of Korean medical insurance. Still now, it is considered that a few more issues should be modified for the most balanced and rational fee schedule in specific situation of Korea. In this article, we analyzed the current Korean medical insurance fee schedule, especially the RBRVS related to rheumatic diseases. And we introduced the guide of the medical service for rheumatic diseases in the view of approved limit under the medical insurance. In addition, the new optional medical service system, which was operated recently, was also evaluated briefly. It is suggested that the medical insurance fee schedule be modified to more acceptable and reasonable one for the best medical services. For that purpose, it is necessary for medical committee and its members to make an efforts continuously on the basis of the great insights of the current fee schedule of Korean medical insurance.

Health-Related Quality of Life in Korean Patients with Rheumatoid Arthritis / 대한류마티스학회지

OBJECTIVE: The objective of this study is to assess the health-related quality of life (HRQOL), to examine the correlation among each measurement, and to identify the predictor for HRQOL in Korean patients with rheumatoid arthritis (RA). METHODS: The HRQOL and clinical and laboratory parameters were assessed by Short Form Health Survey-36 (SF-36), EuroQol5 Dimensions (EQ-5D), time trade off (TTO) and standard gamble (SG) using computer software, Centers for Epidemiologic StudiesDepression (CES-D), social support, self-efficacy scale, Korean Health Assessment Questionnaire (KHAQ), functional class, radiologic classification, morning stiffness, Ritchie index, erythrocyte sedimentation rate (ESR), and c-reactive protein (CRP) respectively from 100 outpatients with RA. And the data of the SF-36 and EQ-5D in RA patients were compared with those in 228 healthy controls. RESULTS: Of the 100 subjects with RA, 93 (93 %) were women with mean age of 51.7+/-9.8 years. The mean years of disease onset were 11.16+/-9.23. The mean scores of SF-36 global health (GH), mental component summary (MCS) and physical component summary (PCS) were 51.5+/-20.6, 61.6+/-26.6, and 47.1+/-24.1, respectively. The mean EQ-5D utility and visual analog scale (VAS) score were 0.58+/-0.3 and 61.7+/-20.5, respectively. The mean scores of the TTO and SG were 0.56+/-0.58 and 0.51+/-0.39. The SF-36 and EQ-5D scores in RA patients were significantly lower than those in healthy controls. The mean scores of 8 KHAQ disability index and visual analog pain scale were 0.83+/-0.65 and 50.0+/-23.7, respectively. The mean scores of CES-D, self-efficacy scale, social support, and social network were 9.67+/-6.76, 68.2+/-15.2, 2.37+/-0.19, and 2.19+/-0.55, respectively. The KHAQ mean score was negatively correlated with the scores of SF-36 GH, MCS, PCS, EQ-5D utility, EQ-5D VAS score, social support, social network (r=-0.62, r=-0.47, r=-0.64, r=-0.60, r=-0.39, r=-0.26, r=-0.36, respectively, all p's<0.001), and self-efficacy scale (r=-0.24, p=0.02), and positively correlated with the CES-D (r=0.61, p<0.001). In multivariate models, the predicting variables of SF-36 GH were KHAQ and self-efficacy scale. The predicting variables of SF-36 MCS were age, KHAQ, and self-efficacy scale and the predicting variables of SF-36 PCS were age, income, KHAQ, and self-efficacy scale. CONCLUSION: These results suggest that HRQOL in Korean patients with rheumatoid arthritis is significantly lower than healthy control. The age, HAQ, CES-D, self-efficacy scale were meaningful variables that was significantly correlated with HRQOL. Therefore, the efforts to improve HRQOL may be designed to improve the self-efficacy and the depression in addition to conventional treatment.

A Case of Recurrent Transient Monocular Blindness in Systemic Lupus Erythematosus patient with Antiphospholipid Antibody Syndrome

Transient monocular blindness (TMB) may occur in patients with systemic lupus erythematosus (SLE). Several mechanisms have been suspected as the causes of such TMBs. A 32-year-old female patient with SLE presented recurrent monocular altitudinal visual field defects lasting for several minutes and occurring less than six times per day. Her anticardiolipin antibody level was persistently positive. All cerebrovascular imagings were normal. We report a case of recurrent TMBs in SLE with antiphospholipid antibody syndrome, which may have been induced by vasospasm.

Sequential Development of Systemic Lupus Erythematosus in a Patient with Juvenile Rheumatoid Arthritis / 대한류마티스학회지

Overlap syndrome is used to describe patients who have two or more well-defined connective tissue diseases. Although a variety of overlap syndromes are now recognized, the coexistence of the progression of juvenile rheumatoid arthritis (JRA) to systemic lupus erythematosus (SLE) is uncommon. We describe a patient who had typical deforming polyarthritis, who years later developed SLE.

A Case of Malignant Lymphoma during Treatment with Methotrexate for Rheumatoid Arthritis / 대한류마티스학회지

Rheumatoid arthritis (RA)is a multisystemic inflammatory disease with a prevalance of approximately 1%of the population.The use of disease modifying anti-rheumatic drug (DMARD)is an essential regimen for the treatment of RA. Among DMARDs,methotrexate (MTX)is used worldwide with confirmed effectiveness.However,cytopenia,pulmonary injury,and hepatic toxicity are a few side effects limiting its use.In addition,although the oncogenic potential of MTX is low,several cases have been reported.Recently an increased risk of developing lymphoproliferative disorders has been reported in patients with RA. The incidence is higher in elderly individuals with severe longstanding seropositive RA,those with Sjogren's or Felty's syndrome,and in patients with RA treated with prolonged low dose MTX.We describe a case of RA who developed non-Hodgkin's lymphoma during low dose MTX therapy.

Lack of Association Between Osteoarthritis of the Knee and Gene Polymorphisms of VDR in Korean Postmenopausal Women / 대한류마티스학회지

OBJECTIVE: To determine whether polymorphisms of the Vitamin D receptor (VDR)gene,known to be associated with osteoporosis and/or osteoarthritis (OA) in Caucasians,might also relate to the risk of OA and osteoporosis in Korean postmenopausal women METHODS: A population of 130 postmenopausal women,including 76 healthy controls and 54 knee OA patients,were studied using anteroposterior radiographs of the knee,which were graded for OA according to the Kellgren classification system.The VDR genotype was determined by using polymerase chain reaction and by digestion with the three restriction enzymes Taq I,Bsm I,and Apa I.Femoral neck bone mineral density (BMD)was assessed in all participants by dual energy X-ray absorptiometry . RESULTS: VDR genotype frequency distributions in Koreans were much different from Caucasian's both in the OA group and the control group.Especially, "t t", "B B" and "A A" genotype were very rare,prominently differentiating from Caucasians.But within Koreans,no significant differences in VDR genotype frequencies were observed between OA cases and controls.VDR genotype was not significantly associated with the radiographic grades of OA.And there were no significant relationships of VDR genotype with BMD scores in each group. CONCLUSION: In Korean postmenoposal women,the VDR gene polymorphisms do not significantly contribute to an increased prevalence of knee OA or to differences in BMD.VDR genotype analysis would not be helpful for assessing the risk of knee OA in Koreans because :(1)there is no correlation of VDR genotypes with the radiographic severity of OA ;and (2)there is a more skewed distribution of VDR genotypes in Korean population compared to the Caucasian's .

Expressions of transforming growth factor beta in patients with rheumatioid arthritis and osteoarthritis

No abstract available.

A Case of Adult Onset Still's Disease Associated with Epstein-Barr Virus / 대한류마티스학회지

Adult onset Still 's disease (AOSD)is a rare,distinct clinical entity which affects predominantly young adults aged 16-35.It affects multiple organs,and at present,the etiology is still unclear.Because this disease has few diagnostic or confirmative test,the diagnosis is made by the differential diagnosis and by excluding other diseases.Several reports have suggested a viral trigger in the pathogenesis of this disease.It has some common clinical features ;abrupt onset, high fever,sore throat,transient maculopapular rash,lymphadenopathy,and hepatosplenomegaly.We describe a 17-year-old man who fulfilled the proposed diagnostic criteria of AOSD and had evidence of acute Epstein-Barr virus infection.He complained of intermittent high fever and myalgia for a week.He also had maculopapular rash,sore throat,multiple right cervical lymphadenopahty, and right ankle pain and swelling.After admission,intermittent fever persisted for a month,but diffuse myalgia and migrating arthralgia fluctuated.